Current methods for sequencing DNA would require hundreds of expensive sequencing machines, hundreds of reaction preparation robot systems, several man-decades of work, and billions of dollars to completely sequence the human genome. There are potentially much higher payoffs in developing new automated large-scale sequencing technologies which can accomplish this goal several orders of magnitude faster and less expensively. The proposed project combines several recent advancements in sequencing- related technologies with high-speed, computer-controlled machinery design in an effort to produce a large-scale sequencing instrument. Using high- throughput automated liquid handling techniques, high-speed electrophoresis, and the on-line primer assembly and directed primer walking techniques developed at Brookhaven National Laboratories (BNL), Intelligent Automation Systems (IAS) will design a completely integrated sequencing instrument which requires very little operator intervention.